Predict genome-scale fluxes based solely on enzyme abundance by a novel Hyper-Cube Shrink Algorithm
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چکیده
One of the long-expected goals of genome-scale metabolic modeling is to evaluate the influence of the perturbed enzymes to the flux distribution. Both ordinary differential equation (ODE) models and the constraint-based models, like Flux balance analysis (FBA), lack of the room of performing metabolic control analysis (MCA) for large-scale networks. In this study, we developed a Hyper-Cube Shrink Algorithm (HCSA) to incorporate the enzymatic properties to the FBA model by introducing a pseudo reaction constrained by enzymatic parameters. Our algorithm was able to handle not only prediction of knockout strains but also strains with quantitative adjustment of expression level or activity. We first demonstrate the concept by applying HCSA to a simplest three-node network. Then we validate its prediction by comparing with ODE and with a synthetic network in Saccharomyces cerevisiae producing voilacein and analogues. Finally we show its capability of predicting the flux distribution in genome-scale networks by applying it to the sporulation in yeast.
منابع مشابه
Genome-scale fluxes predicted under the guidance of enzyme abundance using a novel hyper-cube shrink algorithm
Motivation One of the long-expected goals of genome-scale metabolic modelling is to evaluate the influence of the perturbed enzymes on flux distribution. Both ordinary differential equation (ODE) models and constraint-based models, like Flux balance analysis (FBA), lack the capacity to perform metabolic control analysis (MCA) for large-scale networks. Results In this study, we developed a hyp...
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تاریخ انتشار 2016